New Hope for Alzheimer's Patients?

Working with mice, researchers at Case Western Reserve University School of Medicine are reporting a dramatic discovery in the search for a treatment for Alzheimer’s disease (AD). They treated Alzheimer’s-prone mice with a drug called bexarotene, which is already FDA-approved and available as the anti-cancer drug Targretin®.

The result, reported in the February 10 issue of Science, is nothing short of stunning. Bexarotene appeared to dissolve the excess brain-harming amyloid beta in the mouse brain. Amyloid beta (Aβ) is produced naturally in healthy brains, mouse and human. But when Aβ builds up and forms deposits, it seems to interfere with the function of the brain, including the formation of new memories.

Researchers found that just six hours after administering bexarotene, 25% of the excess Aβ was cleared from the brains of the mice. After 72 hours, 75% of the Aβ plaque was gone and the behavior of the mice was observably different. For more on these finds, take a look at this video released by Case.

So now the big question is this: If bexarotene works like this in mice, will it work the same way in human beings with AD? According to Gary Landreth, professor of neurosciences at Case and lead author of the study, that question is already researched. “We need to be clear; the drug works quite well in mouse models of the disease. Our next objective is to ascertain if it acts similarly in humans. We are at an early stage in translating this basic science discovery into a treatment,” Landreth said in a press release issued by Case.

One interesting point about bexarotene is that it does not act directly on Aβ. What it appears to do is to stimulate the expression of gene, apolipoprotein E or apoE. Bexarotene seems to switch apoE back on to a healthy level, which produces a protein that helps clear Aβ from the cells of the brain.

This discovery about bexarotene is truly exciting news in the field of Alzheimer’s research. In the final sentence of the report in Science, the authors conclude cautiously that “The ability of bexarotene to rapidly reverse a broad range of deficits suggests that…[it] may be of therapeutic utility in the treatment of AD…”

If you know someone dealing with AD—and who doesn’t?—this is a promising advance. It is critical, however, to stress that there are still key questions that must be answered before this finding changes the way AD is treated.

On the positive side, part of the excitement is that bexarotene is already FDA-approved. What about side effect? As the study puts it, bexarotene has “a favorable safety profile.” In other words, we already know that this drug is reasonably safe for human use.

But will it work? And if so, how long will it work in an individual AD patient before the benefits of the drug are no longer strong enough to off-set the progression of the disease?

Time will tell. For now, however, there’s new reason for hope in the face of one of our most dreaded diseases.

The article entitled "ApoE-directed Therapeutics Rapidly Clear β-amyloid and Reverse Deficits in AD Mouse Models” is published in the February 10 issue of Science, the journal of the American Association for the Advancement of Science.